Purpose

The causal relationships between circulating adipokines and idiopathic pulmonary fibrosis (IPF) are yet to be established. We performed a two-sample Mendelian randomization (MR) study to investigate the causal roles of adipokines on IPF risk.

Methods

We analyzed the summary data from genome-wide association studies (GWAS), including adiponectin, leptin, resistin and monocyte chemoattractant protein-1 (MCP-1) and IPF. The inverse-variance weighted (IVW) method was considered as the major method and the MR-Egger, weighted median, simple mode and weighted mode were utilized as complementary methods. We also performed the sensitivity analyses, including heterogeneity test, horizontal pleiotropy test and leave-one-out analysis.

Results

The selected number of single nucleotide polymorphisms (SNPs) was 13 for adiponectin, 6 for leptin,12 for resistin, and 6 for MCP-1, respectively. The results showed a causal effect of the circulating adiponectin levels on the risk of IPF (OR 0.645, 95% CI 0.457–0.911, P = 0.013). However, we did not observe significant associations of genetic changes in serum leptin (OR 1.018, 95% CI 0.442–2.346, P = 0.967), resistin (OR 1.002, 95% CI 0.712–1.408, P = 0.993), and MCP-1 (OR 1.358, 95% CI 0.891–2.068, P = 0.155) with risk of developing IPF. There was no evidence of heterogeneity or horizontal pleiotropy. The sensitivity analyses confirmed that our results were stable and reliable.

Conclusions

The increase in serum adiponectin was associated causally with a decreased risk of developing IPF. There is no evidence to support a causal association between leptin, resistin or MCP-1 with risk of IPF. Further studies are needed to confirm our findings.

中文翻译：

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循环脂肪因子与特发性肺纤维化风险的遗传关联：两样本孟德尔随机研究

目的

循环脂肪因子与特发性肺纤维化（IPF）之间的因果关系尚未确定。我们进行了两个样本的孟德尔随机化 (MR) 研究，以调查脂肪因子对 IPF 风险的因果作用。

方法

我们分析了全基因组关联研究 (GWAS) 的汇总数据，包括脂联素、瘦素、抵抗素和单核细胞趋化蛋白-1 (MCP-1) 和 IPF。以逆方差加权（IVW）方法为主要方法，MR-Egger、加权中位数、简单模式和加权模式为补充方法。我们还进行了敏感性分析，包括异质性检验、水平多效性检验和留一分析。

结果

选择的单核苷酸多态性（SNP）数量分别为脂联素13个、瘦素6个、抵抗素12个和MCP-1 6个。结果显示循环脂联素水平与 IPF 风险存在因果关系（OR 0.645，95% CI 0.457–0.911，P  = 0.013）。然而，我们没有观察到血清瘦素（OR 1.018，95% CI 0.442-2.346， P  = 0.967）、抵抗素（OR 1.002，95% CI 0.712-1.408，P  = 0.993）和MCP-基因变化之间存在显着关联。1（OR 1.358，95% CI 0.891–2.068，P  = 0.155），有发生 IPF 的风险。没有异质性或水平多效性的证据。敏感性分析证实我们的结果稳定可靠。

结论

血清脂联素的增加与发生 IPF 的风险降低有因果关系。没有证据支持瘦素、抵抗素或 MCP-1 与 IPF 风险之间存在因果关系。需要进一步的研究来证实我们的发现。